The principal goals are: a) to develop antisense nucleic acid methodologies for disruption of gene expression in cells of interest in neurobiology; b) to apply these methods to problems of signal transduction, and of ion channel and neurotransmitter reception function. Studies will be carried out in NGF-induced PC-12 cells, with a focus on Na+ and Ca2+ channels, and on their modulation by G protein coupled systems. Problems of interest include the sequence identity of the Ca2+ channel genes expressed and their spatial distribution between neurites and somites. Assays will be by electrophysiology and by sensitive RNA analysis. Additional studies in oocytes will focus on the identification of the epitopes within G proteins that are important for interactions with 7 helix receptors and effectors.